Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients

Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. Chromobox (CBX) family protein expression has been reported in a variety of human malignancies, but the roles of CBXs in ccRCC remain unclear. In this study, by using ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal, and TIMER, we found the transcriptional levels of CBX3 and CBX4 in ccRCC tissues were significantly higher than those in normal kidney tissues, whereas the transcriptional levels of CBX1, CBX5, CBX6, and CBX7 were significantly reduced in ccRCC tissues. The promoters of CBX2, CBX3, CBX4, CBX5, CBX6, CBX7, and CBX8 were hypermethylated, whereas the CBX1 promoter was hypomethylated in ccRCC. The expression of CBX1, CBX3, CBX4, CBX5, CBX6, and CBX7 was significantly associated with clinicopathological parameters in ccRCC patients. ccRCC patients with high expression levels of CBX3, CBX4, and CBX8 and low expression levels of CBX1, CBX5, CBX6, and CBX7 showed a strong association with poor overall survival. Genetic alterations in CBXs were correlated with poor overall survival and disease-free survival in patients with ccRCC. Moreover, we found significant associations between the expression of CBXs and infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Our results provide novel insights into the development of CBX-based biomarkers and therapeutic targets for ccRCC.

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Neutrophil–lymphocyte ratio as a prognostic factor for survival in patients with advanced renal cell carcinoma (Turkish Oncology Group Study)

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219900908 ◽

2020 ◽

Vol 26 (7) ◽

pp. 1583-1589

Author(s):

Mutlu Hizal ◽

Mehmet AN Sendur ◽

Hatime Arzu Yasar ◽

Kadriye Bir Yucel ◽

Cagatay Arslan ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Advanced Renal Cell Carcinoma ◽

Study Group ◽

Poor Overall Survival ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

Background To describe the prognostic value of neutrophil–lymphocyte ratio and its effect on survival in in patients with advanced renal cell carcinoma. Methods We retrospectively analyzed 331 patients. The cut-off value of neutrophil–lymphocyte ratio was specified as “3” which is mostly close—and also clinically easily applicable—to the median neutrophil–lymphocyte ratio level of our study group. High group is identified as neutrophil–lymphocyte ratio >3 (n = 160) and low group is identified as neutrophil–lymphocyte ratio ≤3 (n = 163). Results A total of 331 (with 211 male and 120 female) patients were enrolled to study. The median age of the patients was 58. The International Metastatic RCC Database Consortium risk score is calculated for the 72.8% (n = 241) of the study group and among these patients, favorable, intermediate, and poor risk rates were 22, 45.2, and 32.8%. The total usage of tyrosine kinase inhibitors reached 78% of the patients. The median overall survival was 32 months versus 11 months in the neutrophil–lymphocyte ratio low and high groups, respectively (HR: 0.49 (95% CI 0.37–0.65), p < 0.001). Conclusion In conclusion, the pre-treatment value of elevated neutrophil–lymphocyte ratio might be a predictor of poor overall survival in advanced renal cell carcinoma patients.

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Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients

Modern Pathology ◽

10.1038/s41379-021-00864-0 ◽

2021 ◽

Author(s):

Oscar Brück ◽

Moon Hee Lee ◽

Riku Turkki ◽

Ilona Uski ◽

Patrick Penttilä ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

T Cells ◽

Cell Carcinoma ◽

Renal Cell ◽

Immune Cell ◽

The Cancer Genome Atlas ◽

Poor Overall Survival ◽

Clinicopathologic Characteristics ◽

Peritumoral Tissue

AbstractWhile the abundance and phenotype of tumor-infiltrating lymphocytes are linked with clinical survival, their spatial coordination and its clinical significance remain unclear. Here, we investigated the immune profile of intratumoral and peritumoral tissue of clear cell renal cell carcinoma patients (n = 64). We trained a cell classifier to detect lymphocytes from hematoxylin and eosin stained tissue slides. Using unsupervised classification, patients were further classified into immune cold, hot and excluded topographies reflecting lymphocyte abundance and localization. The immune topography distribution was further validated with The Cancer Genome Atlas digital image dataset. We showed association between PBRM1 mutation and immune cold topography, STAG1 mutation and immune hot topography and BAP1 mutation and immune excluded topography. With quantitative multiplex immunohistochemistry we analyzed the expression of 23 lymphocyte markers in intratumoral and peritumoral tissue regions. To study spatial interactions, we developed an algorithm quantifying the proportion of adjacent immune cell pairs and their immunophenotypes. Immune excluded tumors were associated with superior overall survival (HR 0.19, p = 0.02) and less extensive metastasis. Intratumoral T cells were characterized with pronounced expression of immunological activation and exhaustion markers such as granzyme B, PD1, and LAG3. Immune cell interaction occurred most frequently in the intratumoral region and correlated with CD45RO expression. Moreover, high proportion of peritumoral CD45RO+ T cells predicted poor overall survival. In summary, intratumoral and peritumoral tissue regions represent distinct immunospatial profiles and are associated with clinicopathologic characteristics.

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Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

Oncotarget ◽

10.18632/oncotarget.3445 ◽

2015 ◽

Vol 6 (11) ◽

pp. 9577-9591 ◽

Cited By ~ 19

Author(s):

Yozo Mitsui ◽

Hiroshi Hirata ◽

Naoko Arichi ◽

Miho Hiraki ◽

Hiroaki Yasumoto ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Bone Morphogenetic Protein ◽

Renal Cell ◽

Bone Morphogenetic Protein 2 ◽

Poor Overall Survival ◽

Morphogenetic Protein

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Beta-1,4-galactosyltransferase II predicts poor prognosis of patients with non-metastatic clear-cell renal cell carcinoma

Tumor Biology ◽

10.1177/1010428317691417 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769141 ◽

Cited By ~ 2

Author(s):

Haijian Zhang ◽

Yidong Liu ◽

Huyang Xie ◽

Qiang Fu ◽

Zheng Liu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Recurrence Free Survival ◽

Poor Overall Survival ◽

Cell Renal Cell Carcinoma ◽

Fuhrman Grade ◽

Free Survival

Beta-1,4-galactosyltransferase II is found to be associated with the alterations of tumor-related glycosylation. However, the clinical significance of beta-1,4-galactosyltransferase II in non-metastatic clear-cell renal cell carcinoma has not been reported up to now. Herein, our researches suggested that the expression level of beta-1,4-galactosyltransferase II was first found to be positively associated with tumor size, Fuhrman grade, lymphovascular invasion, rhabdoid differentiation, tumor necrosis and poor overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma, both in training set and validation set. Moreover, beta-1,4-galactosyltransferase II expression was identified as an independent adverse prognosticator for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Ultimately, prognostic accuracy of the nomogram integrating beta-1,4-galactosyltransferase II with other independent prognostic parameters was dramatically improved for overall survival and recurrence-free survival of patients with non-metastatic clear-cell renal cell carcinoma. Taken together, beta-1,4-galactosyltransferase II is a potential independent adverse prognostic factor for postoperative recurrence and survival, which could be developed as a useful biomarker for non-metastatic clear-cell renal cell carcinoma by a series of further independent and retrospective studies, so as to help the postsurgical management of clear-cell renal cell carcinoma patients.

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DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms21082881 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2881

Author(s):

Tsung-Chieh Lin

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Progression ◽

Renal Cell ◽

Biological Effects ◽

The Cancer Genome Atlas ◽

Prognostic Indicators ◽

Rna Helicases ◽

Poor Overall Survival ◽

Expression Levels

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, DDX3X’s role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to DDX3X. The results suggest that DDX3X is epigenetically repressed in tumor tissue and that lower DDX3X is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by DDX3X. Furthermore, SPINK1 and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with DDX3X in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low DDX3X. Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3Xlow/SPINK1high/metallothioneinhigh axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low DDX3X expression levels.

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